Functional and metabolic MRI techniques have been rapidly evolving and have tremendous potential for clinical brain disorders research. Clinical activation fMRI studies are performed at using blood oxygenation level dependent (BOLD) contrast method. Multiple Sclerosis patients and healthy controls were evaluated to determine the activation in the contralateral primary sensorimotor cortex and deactivation (mediated by transcallosal tracts) in the homologous ipsilateral region during a simple hand tapping task. In a multicenter trial conducted at eight European sites using 1.5 Tesla scanners. Brain deactivation during right hand movement was assessed in 56 right-handed patients with relapsing-remitting or secondary progressive MS without clinically evident hand impairment and in 60 age-matched, healthy subjects. The MS patients showed reduced task-associated deactivation relative to healthy controls in the pre- and postcentral gyri of the ipsilateral hemisphere in the region functionally specialised for hand movement control. We hypothesise that this impairment of deactivation is related to deficits of transcallosal connectivity and GABAergic neurotransmission occurring with the progression of pathology in the MS patients. This study has substantially extended previous observations with a well-powered, multicentre study. The clinical significance of these deactivation changes is still uncertain, but the functional anatomy of the affected region suggests that they could contribute to impairments of motor control.